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Received in July 23, 2003.Approved by the Consultive Council and
accepted for publication on December 10, 2004.* Work done at
Academic Teaching Hospital Dresden-Friedrichstadt, Friedrichstrasse
41, 01067 Dresden, Germany.
1 MD., Department of Dermatology at Academic Teaching Hospital
Dresden-Friedrichstadt, Germany 2 MD., Department of Dermatology at
Academic Teaching Hospital Dresden-Friedrichstadt, Germany 3 MD.,
Institute of Pathology "Georg Schmorl"
©2005 by Anais Brasileiros de Dermatologia
Lymphomatoid papulosis - Report of two cases*
Papulose linfomatóide - Relato de dois casos*
Uwe Wollina1 Claudia Wurbs1 Jaqueline Schönlebe2
Abstract: Lymphomatoid papulosis (LP) is a rare variant of
cutaneous T-cell lymphomas withlarge CD30-positive intracutaneous
T-cell infiltrate. There is a discrepancy between
histologysuggesting a highly malignant and aggressive disease and
the chronic relapsing mostly selflimiting course in most cases. We
report two patients. A 64-year-old woman with a 10-year his-tory of
LP was treated with cream PUVA that was able to control the
disease. The other case,a 42-year-old woman had an 18-year history
of LP treated by PUVA and later by extracorporealphotochemotherapy
(ECP). During ECP a rapid metastatic spread developed that could
not becontrolled by polychemotherapy. Eventually she died due to a
central nervous system metas-tasis one year later.Keywords:
Photopheresis; Lymphoma, T-cell, cutaneous; Lymphomatoid papulosis;
PUVA therapy.
Resumo: A papulose linfomatóide (PL) constitui uma variante rara
dos linfomas cutâneosde células T com a presença de amplo
infiltrado intracutâneo de células T positivas paraCD30. O exame
histológico sugestivo de doença altamente maligna e agressiva
opõe-se aocurso crônico-recidivante, muitas vezes auto-limitado,
presente na maioria dos casos. Sãoapresentados os relatos de dois
pacientes. Uma mulher com 64 anos de idade e história de10 anos de
PL recebeu terapia Puva em creme, sendo a doença controlada. No
segundo caso,uma mulher de 42 anos apresentava história de 18 anos
de PL tratada com Puva e, poste-riormente, com fotoquimioterapia
extracorpórea (FEC). Durante a FEC, observou-se rápidadisseminação
metastática que não pôde ser controlada por poliquimioterapia. A
pacientefoi a óbito após um ano, em razão de metástase no sistema
nervoso central.Palavras-chave: Fotoforese; Linfoma cutâneo de
células T; Papulose linfomatóide; TerapiaPUVA.
An Bras Dermatol. 2005;80(2):161-4.
Case Report161
INTRODUCTIONCutaneous T-cell lymphomas (CTCL) cover a
wide range of diseases with different histology andclinical
course. Lymphomatoid papulosis (LP) is arare variant of
CD30-positive CTCL with a relapsingchronic course. The clinical
presentation is a dissem-inated reddish-brownish papulosis that
tends to healleaving hyperpigmented scars. Necrotic changes
mayoccur. The incidence of LP is about 1.2 to 1.9 casesper million
inhabitants. Some reports on LP in chil-dren have been published,
but it seems more com-mon among adults.1
LP has been differentiated based onhistopathology into three
types, A, B, and C.1 Type Arepresents a LP variant of predominant
large cells
mixed with granulocytes, whereas type B is charac-terized by
small to medium sized cerebriformmononuclear cells. Type C is
composed of large pleo-morphic and anaplastic cells without a
significantcontribution of reactive inflammatory cells.2 The
lym-phocytic cells in LP are of clonal T-cell origin.3 Theyusually
express CD30 like Hodgkin cells but lackfascin, an active bundle
protein.4 In contrast to NK-cell lymphomas the large atypical cells
of LP type Aand C do not express CD56.5
There is no standardized treatment, controlledclinical trials
have not been performed. There is someevidence from case reports
and small series that pho-tochemotherapy with psoralen may cause
partial or
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FIGURE 1:Disseminatedpapules andsmall nodules(Patient 1).
complete remission,6 but mixed outcome has alsobeen demonstrated
for photochemotherapy.7,8
We report two patients with a long history of LPand mixed
outcome after photochemotherapy.
CASE REPORTSCase 1
A 64-year-old woman was referred to ourdepartment with a 10-year
history of chronic relapsingreddish-brownish papules. The disease
was limited inits beginning to the neck and the proximal
lowerlimbs. Two years previously a disseminated manifesta-tion
developed on the limbs and the trunk. She suf-fered from burning
sensations. The papules werenon-pruritic.
Coexistent disorders were a chronic ischemicheart disease with
arterial hypertonia, diabetes melli-tus type II, and nodular
struma.
On clinical examination of the whole body,except the face,
disseminated papules and nodules ofvariable size were seen, some of
them covered with acrust (Figure 1). Hyperpigmented maculae and
scarswere also seen.
Several skin biopsies were taken from the trunkand lower limbs.
Histopathologic examination dis-closed a heavy broad dermal
infiltrate consisting oflymphomonocytoid cells including large
cells withatypical nuclei and mitoses (Figure 2).Immunostainings
(PAAP) revealed positivity for CD30(large cells). CD8, and T cell
intracellular antigen TIA1(only some cells), immunostains for
fascin were nega-tive. In addition granulocytes, especially
eosinophilswere intermingled.
162 Wollina U, Wurbs C, Schönlebe J.
An Bras Dermatol. 2005;80(2):161-4.
FIGURE 2: Overview of HE (Patient 1) (20x).
Laboratory investigations: There was a slightincrease of
eosinophil counts (5.6%) and an increasedratio of T4/T8 by flow
cytometry (3.7). No atypicalcells were observed in the circulating
blood.
Ultrasound scan of pelvic and abdominal organsand X-ray of the
thorax did not show any manifestationof the CTCL. There was
evidence of hepatic steatosis.
The diagnosis of LP, type A, was made. We performed cream PUVA
for two weeks and
used a urea-containing ointment in association. Theshort-term
hospital treatment was followed by a four-week course of outpatient
therapy and resulted inimprovement of burning sensations and
partial remis-sion of LP.
Case 2A 42-year-old woman was referred to our
department for treatment of relapsing papulo-nodu-lar lesions on
the limbs and the trunk. She had a his-tory of 18 years of
relapsing self-healing papulosis.Previous treatments such as UVB
and UVA irradiation,PUVA, dapsone, and vidarabine phosphate had
onlytemporary and slight effects, if any.
On examination we observed multiple erythe-matous papules on the
limbs and trunk, some erodedand covered with a crust (Figures 3 and
4).
Several skin biopsies were taken from theselesions that showed a
dense dermal infiltrate com-posed of large, atypical lymphoid cells
mixed witheosinophils and neutrophils. The immunophenotypewas
CD30-positive, CD3-positive, CD4- and CD8-neg-ative (Figures 5 and
6).
Laboratory investigations: There was anincreased ratio of
activated T-cells as shown by fluo-rescent activated cell sorting
analysis (FACS). Routinelab was normal, no atypical cells were
found in theperipheral blood.
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FIGURE 4:Detail offigure 3.
there was disease progression with secondary lymphnode
involvement. Systemic chemotherapy using 1mg vincristine/day and
200 mg ribomustin (day 1 and8) was started with an initial response
of lymph nodemetastases. One year later, the patient died due
tocerebral spread. The case seems to represent a pro-gression of LP
to CD30-positive systemic lymphoma.
DISCUSSION LP is a chronic relapsing CTCL characterized by
self-healing papules and nodules. Histologicallymalignant but
clinically benign was the characteriza-tion Macaulay (1968) gave
this disease.1 Nowadays LPis considered a rare, distinct variant in
the spectrumof CTCL.1,2 Whereas the disease itself shows only
slowprogression there is a cumulative risk of
malignanttransformation of about 15% after 15 years.9
In patient #2 a progression to systemic CD30-positive lymphoma
has been observed. Such a change
Ultrasound scans revealed a lymph nodeenlargement in the axilla.
Computed tomography dis-closed enlarged retrocaval and
aortopulmonarylymph nodes.
Diagnosis of LP, type A, was made.We used extracorporeal
photopheresis with 8-
methoxypsoralen at 0.6 mg/kg body weight with theTherakos ECP
unit (Johnson & Johnson) leading toan intermittent
leukapheresis and ex vivo pho-tochemotherapy. During each treatment
240 mlleukocyte enriched buffy coat was obtained andretransfused.
Treatments were performed on two con-secutive days once a month.
The patient respondedquickly after 3 cycles with a partial
response. ECP wascontinued for further three months but at the
end
Lymphomatoid papulosis - Report of two cases 163
An Bras Dermatol. 2005;80(2):161-4.
FIGURE 3: Disseminated papules, crusted and eroded
lesions(Patient 2).
FIGURE 5: Histopatologic investigation of patient 2 -
overview(D30 - expression) (APAAP technique).
FIGURE 6: Detail of figure 5.
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only a temporary positive effect but later on a progres-sion of
LP to systemic spread was observed. No otherexperience with ECP in
LP has been published yet.
A new treatment option might be bexarotene.Ten patients with LP
have been treated either orally (n= 3) or topically (n = 7) with a
partial response.14
Therefore, bexarotene might be another option in thepalliative
therapy of LP. Once a transition to a moreaggressive lymphoma has
occurred control of diseasecan only be achieved for a limited
time.
LP is a rare disease with important differentialdiagnoses. It
represents a low-grade CTCL with achronic course but needs
monitoring not to overlooka transition to more aggressive forms of
lymphomas.The treatment is not standardized but pho-tochemotherapy
might be an option in controlling thedisease. Other options with
limited experience arelow-dose methotrexate and probably
bexarotene. �
in biologic behaviour can be explained by escape oflymphoma
cells from growth control by transforminggrowth factor (TGF)-beta
and CD30 ligand.10 Majordifferential diagnoses to LP are summarized
in chart 1.
The treatment of LP has yet not been standard-ized. Based on
extensive experience with CTCL multia-gent chemotherapy is only
indicated for patients withfull-blown or developing extracutaneous
disease. It isnever or only rarely indicated for patients with
skin-lim-ited CD30-positive lymphomas. Low-dose methotrexate(≤25 mg
given at one to four week intervals) is an effec-tive and
well-tolerated treatment in LP.11 Hepatic steato-sis and diabetes
mellitus as in patient #1 are a relativecontraindication since
these factors increase the risk ofhepatic side effects including
liver cirrhosis. ECP hasbeen used in CTCL of the mycosis fungoides
and Sézarysyndrome type with some success. It is thought to be
akind of vaccination therapy.12,13 In patient #2, ECP had
164 Wollina U, Wurbs C, Schönlebe J.
An Bras Dermatol. 2005;80(2):161-4.
papulosis: a T-cell dyscrasia with a propensity to transform
into malignant lymphoma. Ann Intern Med. 1995; 122: 210-7.
10. Kadin ME, Levi E, Kempf W. Progression of lymphomatoid
papulosis to systemic lymphoma associated with escape from growth
inhibition by transforming growth factor-beta and CD30 ligand. Ann
NY Acad Sci. 2001; 941: 59-68.
11. Vonderheid EC, Sajjadian A, Kadin ME. Methotrexate is
effective therapy for lymphomatoid papulosis and other primary
cutaneous CD30-positive lymphoproliferative disorders. J Am Acad
Dermatol. 1996; 34: 470-81.
12. Knobler R, Girardi M. Extracorporeal
photochemoim-munotherapy in cutaneous T cell lymphomas. Ann NY Acad
Sci. 2001; 941: 123-38.
13. Wollina U, Kaatz M. Extracorporeal photochemotherapy in
cutaneous T-cell lymphoma. An overview of current status. Int J
Immunopathol Pharmacol Section Dermatol. 2002;14:411-8.
14. Krathen RA, Ward S, Duvic M. Bexarotene is a new treat-ment
option for lymphomatoid papulosis. Dermatology. 2003; 206:
142-7.
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2. Paulli M, Berti E, Rosso R, et al. CD30/Ki-1-positive
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V, Assaf C, et al. Single-cell analysis of CD30+ cells in
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Petrogiannis-Haliotis T, et al. Fascin expression in CD30-positive
cutaneous lymphoproliferative disorders. J
Cutan Pathol. 2002; 29: 295-300.5. Harvell J, Vaseghi M,
Natkunam Y, Kohler S, Kim Y. Large
atypical cells of lymphomatoid papulosis are CD56 -negative: a
study of 18 cases. J Cutan Pathol. 2002; 29: 88-92.
6. Volkenandt M, Kerscher M, Sander C, Meurer M, Röcken M.
PUVA-bath photochemotherapy resulting in rapid clearance of
lymphomatoid papulosis in a child. Arch Dermatol. 1995; 131:
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7. Wolf P, Cohen PR, Duvic M. Ambivalent response of
lym-phomatoid papulosis treated with methoxypsoralen and UVA. J Am
Acad Dermatol. 1994; 30: 1018-20.
8. Wollina U. Lymphomatoid papulosis treated with extra
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9. Cabanillas F, Armitage J, Pugh WC, et al. Lymphomatoid
MAILING ADDRESS: / ENDEREÇO PARA CORRESPONDÊNCIA:Prof. Dr. Uwe
Wollina, MDDepartment of DermatologyAcademic Teaching Hospital
Dresden-FriedrichstadtFriedrichstrasse 4101067 Dresden
GermanyPhone: (49) 351-4801210 / Fax: (49) 351-4801219E-mail:
[email protected]
CHART 1: Major differential diagnoses of lymphomatoid
papulosis
Differential diagnoses Differentiation from LP by:
Pityriasis lichenoides acuta et varioliformis (PLEVA) CD30
negativityPityriasis lichenoides chronica CD30 negativityNK-cell
lymphoma CD56 positivityAnaplastic large cell lymphoma of skin not
self-healingSecondary cutaneous infiltrates by Hodgkin's disease
fascin positivity
